This paper describes genetic investigations of seroreactivity to five common infectious pathogens in the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Antibody titers and seroprevalence were available for 495 to 782 (depending on the phenotype) family members at two time points, approximately 15 years apart, for Chlamydophila pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and herpes simplex virus 2 (HSV-2). Seroprevalence rates indicate that infections with most of these pathogens are common (≥20% for all of them, >80% for H. pylori, CMV, and HSV-1). Seropositive individuals typically remain seropositive over time, with seroreversion rates of <1% to 10% over ∼15 years. Antibody titers were significantly heritable for most pathogens, with the highest estimate being 0.61 for C. pneumoniae. Significant genome-wide linkage evidence was obtained for C. pneumoniae on chromosome 15 (logarithm of odds, LOD score of 3.13). These results demonstrate that individual host genetic differences influence antibody measures of common infections in this population, and further investigation may elucidate the underlying immunological processes and genes involved.